In vivo BMP-7 (OP-1) enhancement of osteoporotic vertebral bodies in an ovine model

Phillips, Frank M.; Turner, A. Simon; Seim, Howard B.; MacLeay, Jennifer M.; Toth, Carol A.; Pierce, Allen R.; Wheeler, Donna L.

doi:10.1016/j.spinee.2006.01.014

Cited by 64 publications

(44 citation statements)

References 21 publications

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“…cumulative rhBMP-2 release was only approximately 38% when GMs had almost completely degraded [10,12] because part of the rhBMP-2 interacted with CPC after delivery from the microspheres and was released very slowly via diffusion [5,24,25]. In our model, the defect did not heal spontaneously after 140 days, which is similar to results reported for an ovine model [23]. Therefore, this bone defect is critical-sized in the osteoporotic model.…”

Section: Discussionsupporting

confidence: 86%

“…Sustained release of BMPs can accelerate bone healing in osteoporosis [3,23]. GMs have been widely used as a controlledrelease carrier of growth factors with good biocompatibility and degradability [12,33].…”

Section: Discussionmentioning

confidence: 99%

“…Second, we cannot ensure the enhanced healing is related only to greater rhBMP-2 release, as improvement in the biomechanical properties could occur from the effect of more rhBMP-2 and faster GM degradation. Third, we evaluated only two times; however, the two times were chosen based on results of previous studies because they were representative of the period of bone healing [17,23].…”

Section: Discussionmentioning

confidence: 99%

“…In an osteoporotic ovine model, BMP-2 cDNA delivered locally by an adenoviral vector accelerated fracture healing of the tibias [3]. In another study, local BMP-7 treatment using factor-loaded PLGA microspheres tended to improve mechanical strength and histomorphometric parameters of osteopenic vertebra [23].…”

Section: Introductionmentioning

confidence: 95%

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Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

Liu

et al. 2010

Clinical Orthopaedics &Amp; Related Research

108

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Background The capacity for bone healing reportedly is limited in osteoporosis with a less than ideal environment for healing of bone grafts. We therefore developed a composite bone substitute with rhBMP-2 loaded gelatin microsphere (GM) and calcium phosphate cement (CPC) to use in osteoporosis. Questions/purposes We asked whether (1) controlled release of rhBMP-2 could be improved in this composite bone substitute and (2) increasing factors released from the bone substitute could accelerate osteoporotic bone healing. Methods We soaked rhBMP-2/GM/CPC and rhBMP-2/ CPC composites in simulated body fluid for 28 days and then determined the amount of rhBMP-2 released. Both composites were implanted in bone defects of osteoporotic goats and left in place for 45 and 140 days; the specimens then were evaluated mechanically (pushout test) and morphologically (CT scanning, histology). Results The in vitro study showed the new composite released more rhBMP-2 compared with rhBMP-2/CPC. CT showed the defects healed more quickly with new grafts. The bone mineralization rate was greater in rhBMP-2/GM/ CPC than in rhBMP-2/CPC after 45 days of implantation and the pushout test was stronger after 45 and 140 days of implantation. Conclusions The new graft composite released more loaded factors and appeared to repair osteoporotic bone defects. Clinical Relevance These preliminary data suggest the new composite can be used as a bone substitute to accelerate healing of fractures and bone defects in osteoporosis.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

Liu

et al. 2010

Clinical Orthopaedics &Amp; Related Research

108

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“…Bone loss has been reported previously at various skeletal sites in sheep following ovariectomy [5,16,27,28,42], chronic steroid therapy [7,10] or dietary manipulation [9], but in none of these studies, could these animals be classified as osteoporotic by standard definitions. Other studies have implemented combination treatments to induce osteoporosis in sheep [13, 14, 19-21, 29, 32, 33] and although such treatments have resulted in further bone loss compared to the single treatments, lumbar spine BMD was either not reduced significantly [13,29,32,33] or it did not achieve the minimum of 25% bone loss [20,21] required to classify them as osteoporotic. The current study was undertaken in an attempt to achieve more substantial bone loss in the lumbar spine of domestic sheep, a large animal that is frequently used for experimental studies.…”

Section: Discussionmentioning

confidence: 99%

Validation of the sheep as a large animal model for the study of vertebral osteoporosis

Zarrinkalam¹,

Beard²,

Schultz

et al. 2008

Eur Spine J

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Rats have long been the animal of choice for research in the field of osteoporosis. In the search for a complementary large animal model the sheep appears useful but hitherto the extent of bone loss from the spine has failed to reach a level that is generally accepted as osteoporotic in humans. Osteoporosis was induced in ten sheep using ovariectomy, low calcium diet and steroid injection for 6 months. Bone samples of iliac crest (IC), lumbar spine (LS), and proximal femur (PF) from the osteoporotic sheep were compared with those from four normal sheep using densitometry, histomorphometry, biochemistry and basic mechanical testing. The differences were examined using an analysis of variance with Tukey-Kramer test. Overall, the bone mineral density at LS and PF decreased more than 25% after treatment. Trabecular bone volume decreased by 29.2, 33.4 and 42.6% in IC, LS and PF, respectively. The failure load of the LS in axial compression was reduced to 2,003 from 6,140 N. The extent of bone loss was sufficient to categorise these sheep as osteoporotic although the pattern of bone loss varied between sites. Reduced mechanical competence in LS confirmed the suitability of this model for evaluation of potential treatments for osteoporosis.

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Current Awareness in Contrast Media and Molecular Imaging

2009

Contrast Media & Molecular

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of Contrast Media and Molecular Imaging. Each bibliography is divided into 15 sections: 1 Reviews; 2 General; Contrast Agents: 3 Chemistry; 4 Technique; 5 Experimental; 6 Applications; Molecular Imaging: 7 Carbon; 8 Fluorine; 9 Gallium; 10 Hydrogen; 11 Indium; 12 Iodine; 13 Phosphorus; 14 Technetium; 15 Others. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

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In vivo BMP-7 (OP-1) enhancement of osteoporotic vertebral bodies in an ovine model

Cited by 64 publications

References 21 publications

Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

Validation of the sheep as a large animal model for the study of vertebral osteoporosis

Current Awareness in Contrast Media and Molecular Imaging

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